Tocotrienols generally are classified as farsnesylated chromanols (FC) and mixed terpenoids. Tocopherol and tocotrienol are believed to have beneficial effects because they act as antioxidants. Tocotrienols, in particular, have been documented to possess hypocholesterolemic effects as well as an ability to reduce atherogenic apolipoprotein B and lipoprotein plasma levels. Further, tocotrienols are believed to be useful in the treatment of cardiovascular disease and cancer. See, for example, Theriault, A., et al., xe2x80x9cTocotrienol: A Review of its Therapeutic Potential,xe2x80x9d Clinical Biochemistry, 32:309-319 (July 1999); and xe2x80x9cTocotrienols: Biological and Health Effects,xe2x80x9d in Antioxidant Status, Diet, Nutrition, and Health, Pappas, ed. (CRC Press), pp. 479-496 (1999). xcex4-tocotrienol and xcex3-tocotrienol, in particular, have been identified as effective suppressants of cholesterol activity, Qureshi, et al., xe2x80x9cResponse of Hypercholesterolemic Subjects to Administration of Tocotrienols,xe2x80x9d Lipids, 30(12) (1995), and in inducing apoptosis of breast cancer cells, Yu, et al., xe2x80x9cInduction of Apoptosis in Human Breast Cancer Cells by Tocopherols and Tocotrienols,xe2x80x9d Nutrition and Cancer, 33(1):26-32 (1999).
Tocols, which includes tocopherols and tocotrienols, have several sources, including several vegetable oils, such as rice bran, soybean, sesame and palm oils. Tocotrienols have been discovered in the seeds of Bixa orellana Linn, otherwise known as the achiote tree. See, Jondiko, I.S., et al., xe2x80x9cTerpenoids and an Apocarotenoid from Seeds of Bixa Orellana,xe2x80x9d Phytochemistry, 28(11):3159-3162 (1989). However, each source of tocotrienols and tocopherols generally contains more than a single tocol homolog. For example, palm oil and rice bran oil generally include both tocotrienols and tocopherols. Further, xcex1-tocopherol has been reported to attenuate certain effects of tocotrienols, such as the cholesterol-suppressive activity of xcex3-tocotrienol. See, for example, Qureshi, et al., supra. In addition, because of their structural similarity, tocotrienols and tocopherols can be difficult to separate.
Geranylgeraniol includes acyclic diterpene alcohols (ADA) and geranylgeraniated terpenoids (GGT), and occurs naturally in linseed oil and cedrela toona wood and tomato fruit. Geranylgeraniol also has been discovered to exist in the seeds of Bixa orellana. See Craveiro, et al., xe2x80x9cThe Presence of Geranylgeraniol in Bixa Orellana Linn,xe2x80x9d Quimica Nova, 12(3):297-298 (1989). Potential uses for geranylgeraniol include synthesis of co-enzyme Q10, vitamin K and tocotrienols. It is believed to inhibit esterification of retinol into inactive retinyl esters and, therefore, may be used to improve skin desquamation and epidermal differentiation. See U.S. Pat. No. 5,756,109, issued to Burger, et al. on May 26, 1998. Geranylgeraniol has been employed in conjunction with HMG-CoA reductase inhibitors in treatment of elevated blood cholesterol. See WO 99/66929 by Scolnick, published Dec. 29, 1999. Geranylgeraniol also is suspected to be useful for treatment of human prostate cancer. See U.S. Pat. No. 5,602,184, issued to Myers, et al. on Feb. 11, 1997. As with isolation of specific tocotrienols, geranylgeraniol must be separated from terpenoid compounds having similar structures when derived from natural sources. Separation of geranylgeraniol from these related compounds can be difficult.
Therefore, a need exists to find a method for recovery of xcex4- and xcex3-tocotrienols, and of geranylgeraniol, that minimizes or overcomes the above-referenced problems.
A source of material known as a byproduct solution of Bixa orellana seed components, which is obtained as an oily material after removing the bulk of annatto color, is removed from either the aqueous extract or solvent extract of annatto seeds. Further, this byproduct contains a tocotrienol component and a geranylgeraniol component and can be used as a source for the recovery of a tocotrienol component and a geranylgeraniol component.
The present invention generally is directed to a method of forming a tocotrienol composition.
The method includes volatilizing solvent from a byproduct solution of Bixa orellana seed components to form thereby a tocotrienol composition.
In one embodiment, the method further includes the step of distilling a geranylgeraniol component of the tocotrienol composition. At least a portion of the geranylgeraniol component is separated thereby from the tocotrienol composition to form a geranylgeraniol distillate.
In another embodiment, the method of forming a tocotrienol composition includes extracting at least a portion of an annatto component from Bixa orellana seeds, whereby an aqueous fraction is formed. The aqueous fraction includes the annatto component, a tocotrienol component and a geranylgeraniol component. The annatto component is precipitated from the aqueous fraction to form an annatto precipitate and a byproduct solution of Bixa orellana seed components. Water then is volatilized from the byproduct solution of Bixa orellana seed components to form the tocotrienol composition.
In still another embodiment, the method includes distilling tocotrienol components of the tocotrienol composition to form a tocotrienol distillate.
The present invention has many advantages. For example, the amount of xcex4-tocotrienol present in the byproduct solution of Bixa orellana seed components employed by the method is very high (500-700 times higher) relative to that found in other common sources, such as palm oil or rice bran oil. Further, and also in contrast to palm and rice bran oils, there is essentially no xcex1-tocopherol present in the byproduct solution of Bixa orellana seed components employed by the method of the present invention. Therefore, the tocotrienol composition formed and, optionally, the tocotrienol distillate formed, generally does not require separation of xcex4-tocotrienol from xcex1-tocopherol which, as discussed above, can have a mitigating effect on the therapeutic properties of xcex4-tocotrienol. Further, the byproduct solution of Bixa orellana seed components is a convenient source of geranylgeraniol. Therefore, relatively high concentrations of geranylgeraniol also can be obtained by the method of the invention.